A 35-year (1966-2000) bibliographic search using the Medline database showed the range of dose involved in adverse reactions was between 1 mg and 36 mg. The adverse reactions were: one patient with autoimmune hepatitis, one case of confusion due to overdose, one case of optic neuropathy, four subjects with fragmented sleep, one psychotic episode, one case of nistagmus, four cases of seizures, one case of headache and two cases of skin eruptions. Attention should be paid on the necessity of enquiring about the drugs that patients are taking, because this product is not harmless for health.- Actas Esp Psiquiatr. 2001 Sep-Oct;29(5):334-7. -- Safety in melatonin use -- Morera AL, Henry M, de La Varga M.

In two weeks after termination of the administration of epiphyseal hormone melatonin, young healthy human volunteers of different chronotypes showed adaptive shifts in heart rate variability.- Eksp Klin Farmakol. 2005 Sep-Oct;68(5):23-5. -- Changes in heart rate variability in healthy humans of different chronotypes under the action of melatonin.

This study advises caution in the uncontrolled use of melatonin in hypertensive patients. The pineal hormone might interfere with calcium channel blocker therapy and should not be considered simply a dietary supplement.- Br J Clin Pharmacol. 2000 May;49(5):423-7. -- Cardiovascular effects of melatonin in hypertensive patients well controlled by nifedipine: a 24-hour study. -- Lusardi P, Piazza E, Fogari R.

The adverse reactions were: one patient with autoimmune hepatitis, one case of confusion due to MLT overdose, one case of optic neuropathy, four subjects with fragmented sleep, one psychotic episode, one case of nistagmus, four cases of seizures, one case of headache and two cases of skin eruptions. Attention should be paid on the necessity of enquiring about the drugs that patients are taking, because this product is not harmless.
- Actas Esp Psiquiatr 2001 Sep-Oct;29(5):334-7 Safety in melatonin use -- Morera AL, Henry M, de La Varga M.

In the absence of sufficient information regarding the longterm safety of exogenous melatonin, the conservative course of action is to restrict melatonin use to those therapeutic applications in which a significant benefit is expected. The decision to ingest melatonin should be preceded by careful consideration of the expected benefits as well as the potential costs of treatment, with recognition of the fact that there has been exaggeration of the benefits and little attention paid to the potential costs in most discussions of this issue to date.
- J Biol Rhythms 1997 Dec;12(6):682-9 -- Reproductive safety of melatonin: a "wonder drug" to wonder about. -- Weaver DR.

Melatonin is available in the United States without prescription, and adverse effects appear to be uncommon. However, because melatonin appears to have immunomodulatory properties, the potential exists for the development of autoimmune-related side effects. We describe a patient in whom characteristic clinical and laboratory features of autoimmune hepatitis developed after beginning melatonin therapy for the treatment of insomnia. Liver biopsy demonstrated histologic features of autoimmune hepatitis. Rapid symptomatic and biochemical improvement resulted from the initiation of immunosuppressive therapy; however, hepatitis recurred after the withdrawal of steroid therapy. The temporal relation observed between melatonin use and the development of autoimmune hepatitis raises the possibility that the drug might be involved in the pathogenesis of this patient's autoimmune disease.- J Clin Gastroenterol 1997 Jul;25(1):376-8 -- Is melatonin associated with the development of autoimmune hepatitis? -- Hong YG, Riegler JL.